HMGB2-RAD21 Axis Promotes Fibro/Adipogenic Progenitor Proliferation and Regulates Fat Infiltration.

Area of Science:

• Muscle biology
• Adipogenesis
• Developmental biology

Background:

• Intermuscular fat (IMF) infiltration impacts muscle health and meat quality.
• The cellular mechanisms controlling intermuscular adipocyte abundance are not fully understood.
• Preadipocyte differentiation in porcine muscle begins postnatally, suggesting embryonic factors are key.

Purpose of the Study:

• To investigate the developmental mechanisms regulating fibro/adipogenic progenitor (FAP) numbers during embryonic stages.
• To identify key cellular players influencing intermuscular adipocyte abundance.
• To explore potential therapeutic targets for managing IMF content.

Main Methods:

• Single-cell RNA sequencing (ScRNA-seq) of embryonic pig muscle.
• Identification and characterization of FAP subpopulations.
• Gene knockout studies (HMGB2) in mice.
• Analysis of FAP proliferation and differentiation potential.

Main Results:

• The first developmental atlas of embryonic FAPs was constructed.
• A distinct HMGB2-expressing FAP subpopulation (FAPs^HMGB2+) was identified as critical for FAP pool size.
• HMGB2 deficiency in mice led to reduced FAP numbers and impaired adipogenesis.
• HMGB2 regulates FAP proliferation in vivo by targeting RAD21, a DNA replication gene.

Conclusions:

• HMGB2 is a key regulator of FAP proliferation and intermuscular adipocyte abundance during development and regeneration.
• Targeting HMGB2 presents a potential strategy for improving pork quality and addressing pathological fat infiltration in skeletal muscle.